Fused human paraoxonase 1 as a prophylactic agent against organophosphate poisoning.

Organophosphates (OPs) are highly neurotoxic compounds and certain OP-compounds are also exploited as a weapon of mass destruction and chemical warfare in terrorist attacks. Available prophylactic and post-exposure treatments are less effective and also have serious side-effects. Thus, there is a dire need to develop effective and safe prophylactic agent(s) against OP-poisoning. Human Paraoxonase 1 (hPON1) can hydrolyze a wide range of OP molecules and can be developed as an effective and safe prophylactic agent. Thus, there is a dire need in the art to develop variant(s) of rhPON1 that not only possess 'good' OP-hydrolyzing activity but also have improved pharmacokinetic properties. In this report, we describe the characterization of the fused hPON1 (FHP) variant that not only exhibit enhanced in vivo pharmacokinetic properties but also delay / prevent the symptoms of OP-poisoning and prevents OP-induced mortality in rats. • rhPON1 can be developed as prophylactic against OP poisoning. • 3dHSA fused rhPON1 (FHP) is developed with improved half-life. • In vivo pharmacokinetic and prophylactic protection efficacy are determined in rat. • FHP provide prophylactic protection against paraoxon-poisoning. [ABSTRACT FROM AUTHOR]